The mechanism of TPN-linked isocitrate dehydrogenase from porcine heart will be studied with the dead-end inhibitor DL-threo-alpha-methylisocitrate. The contribution of TPN-linked isocitrate dehydrogenase activity to various metabolic processes in more intact tissue preparations will be investigated with the aid of the specific inhibitor alpha-methylisocitrate. The mechanism of aconitase from liver and heart will be studied with a number of substrate analogues to determine the identities of the citrate and isocitrate binding sites. The specificity of homogeneous DPN-linked isocitrate dehydrogenase will be investigated with analogues of the cosubstrate and the allosteric effector ADP.